Colloid &  Nanoscience  Journal

Colloid & Nanoscience Journal

Development of L-Aspartic Acid-Grafted Methyl Cellulose Nanocarriers for pH-Responsive and Sustained Delivery of Curcumin

Document Type : Original Article

Author
Dipartimento di Chimica "Ugo Schiff" (DICUS) - Università degli Studi di Firenze, Via della Lastruccia, 3, 50019 Sesto Fiorentino FI
Abstract
Curcumin is a natural bioactive compound with remarkable therapeutic potential; however, its poor aqueous solubility and limited bioavailability have hindered its clinical application. In this study, biodegradable L-aspartic acid-grafted methyl cellulose (MC-g-Asp) nanoparticles were successfully developed as a pH-responsive nanocarrier for the sustained delivery of curcumin. The synthesized nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), zeta potential analysis, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC), confirming successful grafting, efficient drug encapsulation, favorable colloidal stability, and enhanced thermal stability. In vitro release studies revealed a biphasic release profile consisting of an initial burst release followed by sustained drug release, reaching approximately 89% at pH 5.5 and 68% at pH 7.4 after 72 h. Drug release kinetics were best described by the Korsmeyer–Peppas model, indicating an anomalous transport mechanism governed by both diffusion and polymer relaxation. MTT assay demonstrated excellent biocompatibility of the blank nanocarrier, while curcumin-loaded nanoparticles exhibited significant concentration- and time-dependent cytotoxicity against MCF-7 breast cancer cells, with an IC₅₀ of approximately 92 μg mL⁻¹ after 48 h. These findings demonstrate that MC-g-Asp nanoparticles represent a promising biodegradable platform for pH-responsive and sustained curcumin delivery with potential applications in anticancer therapy.

Graphical Abstract

Development of L-Aspartic Acid-Grafted Methyl Cellulose Nanocarriers for pH-Responsive and Sustained Delivery of Curcumin
Keywords

[1] S.J. Hewlings, D.S. Kalman, Curcumin: A review of its effects on human health, Foods 6 (2017) 92. https://doi.org/10.3390/foods6100092.
[2] A.K. Azad, J. Lai, W.M.A.W. Sulaiman, H. Almoustafa, S.A. Alshehade, V. Kumarasamy, V. Subramaniyan, The fabrication of polymer-based curcumin-loaded formulation as a drug delivery system: An updated review from 2017 to the present, Pharmaceutics 16 (2024) 160.
http://doi.org/10.3390/pharmaceutics16020160
[3] S. Pan-On, P. Dilokthornsakul, W. Tiyaboonchai, Trends in advanced oral drug delivery systems for curcumin, Journal of Controlled Release 348 (2022) 335–345.
http://doi.org/10.1016/j.jconrel.2022.05.048
[4] M. Jiang, Y. Gan, Y. Li, Y. Qi, Z. Zhou, X. Fang, J. Jiao, X. Han, W. Gao, J. Zhao, Protein–polysaccharide-based delivery systems for enhancing the bioavailability of curcumin: A review, International Journal of Biological Macromolecules 250 (2023) 126153.
http://doi.org/10.1016/j.ijbiomac.2023.126153
[5] H.S. Abbo, D.M. Yufanyi, T. Shah, N.G. Khaligh, S. Chinnam, T. Efferth, S.J.J. Titinchi, Curcuminoid nanovesicles as advanced therapeutics, ChemBioEng Reviews 10 (2023) 1083–1109. http://doi.org/10.1002/cben.202200047
[6] N. Chelimela, R.R. Alavala, S.R. Satla, Curcumin – bioavailability enhancement by prodrug approach and novel formulations, Chemistry & Biodiversity 21 (2024) e202302030.
http://doi.org/10.1002/cbdv.202302030
[7] C. Wen, L. Cao, Z. Yu, et al., Advances in lipo-solubility delivery vehicles for curcumin: bioavailability, precise targeting, possibilities and challenges, Critical Reviews in Food Science and Nutrition 64 (2024) 10835–10854. http://doi.org/10.1080/10408398.2023.2229433
[8] R. Chang, L. Chen, M. Qamar, et al., The bioavailability, metabolism and microbial modulation of curcumin-loaded nanodelivery systems, Advances in Colloid and Interface Science 318 (2023) 102933. http://doi.org/10.1016/j.cis.2023.102933
[9] Christ H-A, Bourgat Y, Menzel H. Optimization of Critical Parameters for Carbodiimide Mediated Production of Highly Modified Chitosan. Polymers. 2021; 13(16):2702. https://doi.org/10.3390/polym13162702
[10] Siepmann, J.; Siepmann, F. Mathematical modeling of drug delivery. Int. J. Pharm. 364 (2008) 328–343. https://doi.org/10.1016/j.ijpharm.2008.09.004
[11] Dash, S., Murthy, P.N., Nath, L., Chowdhury, P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol. Pharm. 67 (2010) 217–223.
[12] Siepmann, J., Siepmann, F. Mathematical modeling of drug delivery. Int. J. Pharm. 364 (2008) 328–343. 
https://doi.org/10.1016/j.ijpharm.2008.09.004
[13] Costa, P., Sousa Lobo, J.M. Modeling and comparison of dissolution profiles. Eur. J. Pharm. Sci. 13 (2001) 123–133. 
https://doi.org/10.1016/S0928-0987(01)00095-1
[14] Higuchi, T. Mechanism of sustained-action medication. J. Pharm. Sci. 52 (1963) 1145–1149. 
https://doi.org/10.1002/jps.2600521210
[15] Korsmeyer, R.W., Gurny, R., Doelker, E., Buri, P., Peppas, N.A. Mechanisms of solute release from porous hydrophilic polymers. Int. J. Pharm. 15 (1983) 25–35. 
https://doi.org/10.1016/0378-5173(83)90064-9
[16] Peppas, N.A., Sahlin, J.J. A simple equation for the description of solute release. III. Coupling of diffusion and relaxation. Int. J. Pharm. 57 (1989) 169–172. 
https://doi.org/10.1016/0378-5173(89)90306-2
[17] Ritger, P.L., Peppas, N.A. A simple equation for description of solute release. II. Fickian and anomalous release from swellable devices. J. Control. Release 5 (1987) 37–42. 
https://doi.org/10.1016/0168-3659(87)90035-6

[18] Siepmann, J., Peppas, N.A. Higuchi equation: Derivation, applications, use and misuse. Int. J. Pharm. 418 (2011) 6–12. 
https://doi.org/10.1016/j.ijpharm.2011.03.051
[19] Li, Q., et al. Poly(aspartic acid)-based pH-responsive targeting co-delivery nanoparticles. Journal of Biomaterials Applications 36 (2021) 579–591. DOI: 10.1177/0885328220988071.
[20] Stuart, B.H., Infrared Spectroscopy: Fundamentals and Applications, John Wiley & Sons, 2004.
[21] Socrates, G., Infrared and Raman Characteristic Group Frequencies: Tables and Charts, 3rd ed., Wiley, 2001.
 [22] Hatakeyama, T., Hatakeyama, H., Thermal Analysis: Fundamentals and Applications to Polymer Science, Springer, 1998.
[23] Wunderlich, B., Thermal Analysis of Polymeric Materials, Springer, 2005.
[24] Kaczmarek, B., et al., Bacterial Cellulose–Carboxymethylcellulose Composite Loaded with Turmeric Extract for Wound Dressing Applications, Polymers 15 (2023) 320. 
https://doi.org/10.3390/polym15020320
[25] Tonnesen, H.H., Karlsen, J., Studies on Curcumin and Curcuminoids, Z. Lebensm. Unters. Forsch. A 180 (1985) 132–134. 
https://doi.org/10.1007/BF01042730
[26] Afzali, E., et al. Cytotoxicity Effects of Curcumin Loaded on Chitosan Alginate Nanospheres. Int. J. Nanomedicine 16 (2021) 579–589.
[27] A.K. Azad, J. Lai, W.M.A. Wan Sulaiman, H. Almoustafa, S.A. Alshehade, V. Kumarasamy, V. Subramaniyan, The fabrication of polymer-based curcumin-loaded formulation as a drug delivery system: An updated review from 2017 to the present, Pharmaceutics 16 (2024) 160.
http://doi.org/10.3390/pharmaceutics16020160
[28] S. Pan-On, P. Dilokthornsakul, W. Tiyaboonchai, Trends in advanced oral drug delivery systems for curcumin, Journal of Controlled Release 348 (2022) 335–345.
http://doi.org/10.1016/j.jconrel.2022.05.048
[29] M. Jiang, Y. Gan, Y. Li, Y. Qi, Z. Zhou, X. Fang, X. Han, W. Gao, J. Zhao, Protein–polysaccharide-based delivery systems for enhancing the bioavailability of curcumin: A review, Int. J. Biol. Macromol. 250 (2023) 126153. 
http://doi.org/10.1016/j.ijbiomac.2023.126153
[30] Li, Q., et al. Poly(aspartic acid)-based pH-responsive targeting co-delivery nanoparticles. J. Biomater. Appl. 36 (2021) 579–591. 
https://doi.org/10.1177/0885328220988071
 
 
Volume 4, Issue 2
In Press
Summer 2026

  • Receive Date 06 July 2026
  • Revise Date 17 August 2026
  • Accept Date 18 August 2026